Cultural heritage structures may be subjected to exceptional loading conditions such as soil settlements and seismic actions. Consequences of such damage-induced scenarios may not be limited to economic losses but may also hinder building functionality or significantly compromise structural behaviour and safety. Early detection of structural damage via structural health monitoring (SHM) therefore holdssubstantial implications for the risk assessment and the management of cultural heritage buildings. However, the relationship between structural performance – e.g., in terms of scale and severity of damage – and the characteristics of imposed hazards such as settlement distribution and seismic loading is inherently complex, making the design and setup of a dedicated SHM system a challenging task. Hence, this paper lays the groundwork for a novel methodology,  specific for strategic cultural heritage structures, aimed at combining advanced numerical simulations in continuum by means of a Finite element Method (FEM) and in discontinuum by exploiting the Applied Element Method (AEM) to: (i) guide SHM system design by detecting potential damage-sensitive regions within the structure; (ii) gather engineering judgement with regards to expected structural behaviour and possible failure modes; (iii) train surrogate models, aimed at developing more robust correlations between structural performance and hazard characteristics.